Asymmetric hydrogenation using monodentate phosphoramidite ligands.

Area of Science:

• Organometallic Chemistry
• Asymmetric Catalysis
• Green Chemistry

Background:

• Monodentate phosphoramidites are effective ligands for Rh-catalyzed asymmetric hydrogenation.
• Previous methods required extensive ligand optimization for high enantioselectivity.

Purpose of the Study:

• To develop highly enantioselective and efficient catalytic systems for asymmetric hydrogenation using monodentate phosphoramidites.
• To explore the use of modular ligand libraries and mixed catalysts for broader substrate scope and improved performance.

Main Methods:

• Asymmetric hydrogenation of various substituted olefins including dehydroamino acids, itaconic acid derivatives, and cinnamic acids using Rh and Ir catalysts.
• Development and application of a chiral iridium catalyst with a single bulky phosphoramidite ligand (MonoPhos).
• Synthesis and screening of parallel ligand libraries for rapid catalyst optimization.

Main Results:

• Achieved high enantioselectivities (95-99%) for a wide range of substrates.
• Developed an iridium catalyst demonstrating excellent enantioselectivity for acetylated dehydroamino acid esters.
• Demonstrated high turnover frequencies (250-1600 h⁻¹) with enantioselectivity independent of hydrogen pressure.
• Showcased the effectiveness of parallel ligand synthesis and mixed catalyst systems (e.g., phosphoramidite/phosphine) for enhanced performance.

Conclusions:

• Monodentate phosphoramidites are versatile and highly effective ligands for asymmetric hydrogenation.
• The modular ligand library approach and mixed catalyst systems offer efficient routes to optimize catalysts for industrial applications.
• DSM successfully utilizes these MonoPhos ligands for the production of pharmaceutical intermediates.